Safety Trial of NK Cell DLI 3-5/6 Family Member Following Nonmyeloablative ASCT

NCT ID: NCT00586703

Last Updated: 2014-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2013-11-30

Brief Summary

Evaluate the safety of natural killer (NK) cell infusion using CD56 monoclonal antibody selected with Miltenyi Biotec system following nonmyeloablative stem cell transplantation (SCT) from mismatched donors. This pilot study will evaluate toxicity including mortality, occurrence of acute graft versus host disease (aGVHD) and other severe toxicity.

Detailed Description

The use of non-selected donor lymphocyte infusions (DLIs) (to help early immune recovery and induce antitumor response) following nonmyeloablative allogeneic stem cell transplantation (ASCT) is also complicated by the risk of acute graft versus host disease (aGVHD) with 30-40% of patients experiencing grade III-IV aGVHD. Data suggests that the use of natural killer (NK) cells (instead of nonselected DLIs) in this setting may mediate a graft versus tumor (GVT) effect independently of aGVHD.

This pilot study is designed to evaluate the efficacy and toxicity of donor natural killer (NK) cell selection and infusion following nonmyeloablative allogeneic stem cell transplantation from mismatched donors.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NK-CD56

NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors

Group Type: EXPERIMENTAL

NK-CD56

Intervention Type: DEVICE

NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.

Interventions

NK-CD56

NK Cell infusion using CD56 monoclonal antibody following nonmyeloablative SCT from mismatched donors: The cells from leukapheresis will be NK selected using a CD56 antibody and a cell column system provided by Miltenyi Biotec. The target cell dose for each NK cell infusion will be up to 1 X 10(7) CD56+ cells/kg patient weight with less than 0.5 X 10(6) CD3+ cells/kg patient weight. The first NK cell infusion will be administered 6 weeks post transplant in patients who have ≤ grade II aGVHD at the time of infusion. Patients will be evaluated for toxicity and response until 20 weeks after the last NK Infusion.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients with who have undergone a non-myeloablative allogeneic transplant, using a 3-5/6 HLA matched sibling donor. Measureable disease is not needed at study entry.
• Performance status must be Karnofsky 50-100%.
• Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure.
• ≤ Grade 2 acute GVHD at time of infusion of NK cell infusion. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned NKI). The dosage/level of immunosuppressive therapy at the time of NKI should be no greater than 1 mg/kg of prednisone daily or mycophenolate 1000 mg bid daily or cyclosporine with a target level of 200 or equivalent.
• Estimated survival at least 8 weeks.
• Age > or equal to 18 years of age.

Exclusion Criteria

• Pregnant or lactating women,
• Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
• Patients who had biopsy proven overall Grade 4 GVHD lasting longer than 7 days, from the non-myeloablative therapy, are not eligible

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

David Rizzieri, MD

OTHER

Sponsor Role: lead

Responsible Party

David Rizzieri, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David Rizzieri, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University Health Systems

Locations

Duke University Health Systems

Durham, North Carolina, United States

Countries

United States

References

Rizzieri DA, Storms R, Chen DF, Long G, Yang Y, Nikcevich DA, Gasparetto C, Horwitz M, Chute J, Sullivan K, Hennig T, Misra D, Apple C, Baker M, Morris A, Green PG, Hasselblad V, Chao NJ. Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2010 Aug;16(8):1107-14. doi: 10.1016/j.bbmt.2010.02.018. Epub 2010 Feb 24.

Reference Type: RESULT

PMID: 20188202 (View on PubMed)

Other Identifiers

Pro00005123

Identifier Type: -

Identifier Source: org_study_id